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[Effect of indoprofen on biliary secretion in the rat].

The activity of indoprophen on biliary secretion of rats has been investigated. Indoprophen, at a dose of 20 mg/kg induces a marked choleretic effect. It has been hypothesized that the choleretic action of indoprophen could be attributed to an inhibition of prostaglandin-synthetase and to an increase of cAMP which is the physiological factor responsible of ductal choleresis.

Animals↗

Antioxidant activity and inhibition of human neutrophil oxidative burst mediated by arylpropionic acid non-steroidal anti-inflammatory drugs.

It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. Therefore, the aim of the present work was to evaluate and compare the potential scavenging activity for an array of ROS (O2*-, H2O2, HO*, ROO* and HOCl) and RNS (*NO and ONOO-) using in vitro non-cellular screening systems as well as a cellular screening system (human neutrophil oxidative burst), mediated by the arylpropionic acid derivatives (APAs) NSAIDs ibuprofen, flurbiprofen, fenoprofen, fenbufen, ketoprofen, naproxen and indoprofen. The results obtained in the present work demonstrate that under the present experimental conditions, many of the studied APA NSAIDs showed O2*- scavenging activity (fenbufen approximately equal to flurbiprofen approximately equal to indoprofen approximately equal to ketoprofen), H2O2 (ketoprofen approximately equal to indoprofen approximately equal to fenbufen>flurbiprofen>naproxen), HO* (fenoprofen approximately equal to ibuprofen>fenbufen approximately equal to flurbiprofen>ketoprofen>indoprofen approximately equal to naproxen), *NO (indoprofen>naproxen), ONOO- (indoprofen>naproxen>fenoprofen approximately equal to flurbiprofen approximately equal to ibuprofen), as well as inhibit myeloperoxidase (MPO) activity (indoprofen) and scavenge human neutrophil derived ROS (ketoprofen>indoprofen>fenbufen>flurbiprofen). The observed effects, if confirmed in vivo, may strongly contribute to the anti-inflammatory therapeutical activity observed with these NSAIDs.

Acridines↗

Phase behavior of amorphous molecular dispersions II: Role of hydrogen bonding in solid solubility and phase separation kinetics.

PURPOSE: To determine the factors influencing "solid solubility" and phase separation kinetics of drugs from amorphous solid dispersions. METHODS: Solid dispersions of griseofulvin-poly(vinyl pyrrolidone) (PVP) and indoprofen-PVP were prepared using solvent evaporation technique. Dispersions demonstrating single Tg were exposed to 40 degrees C/69% RH for 90 days. Drug solid solubility in the polymer and phase separation rates were determined from changes in Tg of solid dispersions. FTIR spectroscopy and XRD were used to characterize drug-polymer interactions and drug crystallinity, respectively. RESULTS: Freshly prepared solid dispersion of up to 30% w/w griseofulvin and indoprofen were molecularly miscible with PVP. Hydrogen bonding was evident in indoprofen-PVP, but not in griseofulvin-PVP dispersions. When exposed to 40 degrees C/69% RH, griseofulvin phase separated completely, whereas the solid solubility of indoprofen was determined as 13% w/w. The first-order rate constants of phase separation for 10%. 20%, and 30% w/w griseofulvin dispersions were estimated as 4.66, 5.19, and 12.50 (x10(2)) [day(-1)], and those of 20% and 30% w/w indoprofen dispersions were 0.62 and 1.25 (x10(2)) [day(-1)], respectively. CONCLUSIONS: Solid solubility of griseofulvin and indoprofen in PVP is approximately 0% w/w and approximately 13% w/w, respectively. Drug-polymer hydrogen bonding in indoprofen-PVP dispersions favors solid solubility. Phase separation rate of drug from the solid dispersions depends on the initial drug content and the nature of drug-polymer interactions.

Hot Temperature↗

Effect of some cyclooxygenase inhibitors on the increase in guanosine 3':5'-cyclic monophosphate induced by NO-donors in human whole platelets.

1. The effect of the NSAIDs indomethacin, indoprofen, diclofenac and acetylsalicylic acid on the increase in guanosine 3':5'-cyclic monophosphate (cyclic GMP) induced by nitric oxide-donor agents was tested in human whole platelets and in platelet crude homogenate. 2. In whole platelets, indomethacin reduced the increase in cyclic GMP induced by the nitric oxide-donors (NO-donors) sodium nitroprusside (NaNP) and S-nitroso-N-acetylpenicillamine (SNAP) in a dose-dependent way, its IC50 being 13.7 microM and 15.8 microM, respectively. 3. Of the other cyclooxygenase inhibitors tested, only indoprofen reduced the increase in cyclic GMP induced by both NO-donors in a dose-dependent way (IC50=32.7 microM, NaNP and 25.0 microM, SNAP), while acetylsalicylic acid (up to 1000 microM) and diclofenac (up to 100 microM) were ineffective. 4. However, in platelet crude homogenate neither indomethacin nor indoprofen reduced the cyclic GMP production. 5. Indomethacin (10 microM), indoprofen (30 microM), diclofenac (100 microM) and acetylsalicylic acid (1000 microM) showed a comparable efficacy in inhibiting platelet thromboxane B2 (TXB2) production, suggesting that the inhibitory effect of indomethacin and indoprofen on the increase in cyclic GMP induced by both NO-donors was not mediated by inhibition of cyclooxygenase. 6. In vitro, the NSAIDs analysed did not interfere with nitrite production of SNAP. 7. The unhomogeneous behaviour of NSAIDs on the increase in cyclic GMP induced by NO-donors in whole platelets may contribute to the different pharmacological and toxicological characteristics of the drugs, providing new knowledge on the effect of indomethacin and indoprofen.

Acetophenones↗

Antimigraine drugs in the management of daily chronic headaches: clinical profiles of responsive patients.

Flunarizine, a Ca-antagonist with demonstrated antimigraine properties, and indoprofen, an anti-inflammatory non-steroidal agent, were used in the treatment of daily chronic headache. Forty-two migraineurs with interval headache (MIH) were treated with flunarizine in a 6-month open trial, while indoprofen was administered to 23 patients with MIH and 7 with chronic tension headache (CTH) in a 2-month, double-blind, cross-over placebo-controlled study. Flunarizine was found effective in over 65% of the patients, while indoprofen was able to improve headache severity in only 30% of the subjects. In the responder patients, the effectiveness of both drugs is more pronounced in MIH, and seems to be ascribable to the ability of the treatments to reduce number and severity of attacks. A higher incidence of previous affective disturbances is found in non-responsive cases. The analysis of factors converting episodic into chronic headache shows slight but not significant differences between responders and non-responders. An impairment of plasma beta-endorphin levels, in the presence of normal ACTH, cortisol and nociceptive RIII threshold values, characterizes daily chronic headache (DCH) patients. Moreover, indoprofen does not significantly affect these biological and neurophysiological parameters independently of the therapeutic response.

Adult↗

Effect of analgesic agents on emptying of the gallbladder in man.

A controlled study of the clinical pharmacology of the biliary tract has been made. The rate of gallbladder emptying induced by a fatty meal was taken as a parameter for assessment of the inhibitory effect of indoprofen, a new analgesic-anti-inflammatory drug, pentazocine and morphine. The compounds were administered as single doses by iv (indoprofen and pentazocine) or im (morphine) injection. Indoprofen up to 400 mg had no effect, whereas morphine and pentazocine exerted a significant inhibitory effect on emptying of the gallbladder. Adverse reactions of clinical significance were associated with morphine and pentazocine, but were negligible with indoprofen.

Adult↗

Biliary colic as a model for assessing analgesic activity in man.

Acute pain from biliary colic is a model of pathological pain suitable for pharmacological investigations. It has been found useful for assaying analgesic effect of a narcotic-type agent (pentazocine) and a non-narcotic drug (indoprofen), both given intravenously in a single dose. Differences in pain intensity scores assessed on a five-point scale were taken as measurement of the pain-relieving effect. Distribution-free methods were used to estimate the potency ratio of the tested drugs. The analgesic potency of indoprofen based both on total and peak effect was roughly one-tenth that of pentazocine on a weight-for-weight basis. No adverse reactions were associated with indoprofen and a few were found after pentazocine.

Adult↗

Effect of different parameters on the binding of two anti-inflammatory drugs to human serum albumin.

The binding to human serum albumin of two anti-inflammatory drugs, indomethacin and indoprofen, has been studied by chromatographic and spectroscopic techniques. The results shown indicate that the binding of both drugs--but more notably of indoprofen--is very sensitive to variations of the environmental conditions. The binding is also dependent upon limited modifications in the tertiary structure of the protein. The evidences shown tend to indicate that these two phenomena are related, and that the binding is permitted under conditions of a relatively open structure of the protein molecule.

Chromatography, Gel↗